Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, Texas.
Cancer Prev Res (Phila). 2021 Jul;14(7):729-740. doi: 10.1158/1940-6207.CAPR-20-0303. Epub 2021 Apr 23.
Early detection of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcomes; however, PDAC is usually diagnosed late. Therefore, blood-based minimally invasive biomarker assays for limited volume clinical samples are urgently needed. A novel miRNA profiling platform (Abcam Fireplex-Oncology Panel) was used to investigate the feasibility of developing early detection miRNA biomarkers with 20 μL plasma from a training set (58 stage II PDAC cases and 30 controls) and two validation sets (34 stage II PDAC cases and 25 controls; 44 stage II PDAC cases and 18 controls). miR-34a-5p [AUC = 0.77; 95% confidence interval (CI), 0.66-0.87], miR-130a-3p (AUC = 0.74; 95% CI, 0.63-0.84), and miR-222-3p (AUC = 0.70; 95% CI, 0.58-0.81) were identified as significantly differentially abundant in plasma from stage II PDAC versus controls. Although none of the miRNAs individually outperformed the currently used serologic biomarker for PDAC, carbohydrate antigen 19-9 (CA19-9), combining the miRNAs with CA 19-9 improved AUCs from 0.89 (95% CI, 0.81-0.95) for CA 19-9 alone to 0.92 (95% CI, 0.86-0.97), 0.94 (95% CI, 0.89-0.98), and 0.92 (95% CI, 0.87-0.97), respectively. Gene set enrichment analyses of transcripts correlated with high and low expression of the three miRNAs in The Cancer Genome Atlas PDAC sample set. These miRNA biomarkers, assayed in limited volume plasma together with CA19-9, discriminate stage II PDAC from controls with good sensitivity and specificity. Unbiased profiling of larger cohorts should help develop an informative early detection biomarker assay for diagnostic settings. PREVENTION RELEVANCE: Development of minimally invasive biomarker assays for detection of premalignant disease and early-stage pancreatic cancer is key to improving patient survival. This study describes a limited volume plasma miRNA biomarker assay that can detect early-stage resectable pancreatic cancer in clinical samples necessary for effective prevention and clinical intervention.
早期检测胰腺导管腺癌（PDAC）是改善患者预后的关键；然而，PDAC 通常诊断较晚。因此，迫切需要用于有限量临床样本的基于血液的微创生物标志物检测。使用新型 miRNA 分析平台（Abcam Fireplex-Oncology Panel），从训练集（58 例 II 期 PDAC 病例和 30 例对照）和两个验证集（34 例 II 期 PDAC 病例和 25 例对照；44 例 II 期 PDAC 病例和 18 例对照）的 20μL 血浆中，研究了开发早期检测 miRNA 生物标志物的可行性。miR-34a-5p[AUC=0.77；95%置信区间（CI），0.66-0.87]、miR-130a-3p（AUC=0.74；95%CI，0.63-0.84）和 miR-222-3p（AUC=0.70；95%CI，0.58-0.81）在 II 期 PDAC 与对照组的血浆中差异显著。尽管这些 miRNA 中的任何一个都不能单独优于目前用于 PDAC 的血清生物标志物糖链抗原 19-9（CA19-9），但将 miRNA 与 CA19-9 结合使用，可使 CA19-9 单独的 AUC 从 0.89（95%CI，0.81-0.95）提高到 0.92（95%CI，0.86-0.97）、0.94（95%CI，0.89-0.98）和 0.92（95%CI，0.87-0.97）。在 The Cancer Genome Atlas PDAC 样本集中，对与这三个 miRNA 高表达和低表达相关的转录本进行了基因集富集分析。这些 miRNA 生物标志物与 CA19-9 一起在有限量的血浆中检测，可对 II 期 PDAC 与对照组进行有效区分，具有良好的敏感性和特异性。对更大队列的无偏分析应该有助于开发用于诊断的有意义的早期检测生物标志物检测。预防相关性：开发用于检测癌前病变和早期胰腺癌的微创生物标志物检测对于提高患者生存率至关重要。本研究描述了一种有限量血浆 miRNA 生物标志物检测方法，可在临床样本中检测到可切除的早期胰腺癌，这对于有效的预防和临床干预至关重要。
